Comparison of prognosis and postoperative morbidities between standard pancreaticoduodenectomy and the TRIANGLE technique for resectable pancreatic ductal adenocarcinoma.

BACKGROUND: Radical surgery combined with systemic chemotherapy offers the possibility of long-term survival or even cure for patients with pancreatic ductal adenocarcinoma (PDAC), although tumor recurrence, especially locally, still inhibits the treatment efficacy. The TRIANGLE technique was introduced as an extended dissection procedure to improve the R0 resection rate of borderline resectable or locally advanced PDAC. However, there was a lack of studies concerning postoperative complications and long-term outcomes of this procedure on patients with resectable PDAC. AIM: To compare the prognosis and postoperative morbidities between standard pancreaticoduodenectomy (PD) and the TRIANGLE technique for resectable PDAC. METHODS: Patients with resectable PDAC eligible for PD from our hospital between June 2018 and December 2021 were enrolled in this retrospective cohort study. All the patients were divided into PDstandard and PDTRIANGLE groups according to the surgical procedure. Baseline characteristics, surgical data, and postoperative morbidities were recorded. All of the patients were followed up, and the date and location of tumor recurrence, and death were recorded. The Kaplan-Meier method and log-rank test were used for the survival analysis. RESULTS: There were 93 patients included in the study and 37 underwent the TRIANGLE technique. Duration of operation was longer in the PDTRIANGLE group compared with the PDstandard group [440 (410-480) min vs 320 (265-427) min] (P = 0.001). Intraoperative blood loss [700 (500-1200) mL vs 500 (300-800) mL] (P = 0.009) and blood transfusion [975 (0-1250) mL vs 400 (0-800) mL] (P = 0.009) were higher in the PDTRIANGLE group. There was a higher incidence of surgical site infection (43.2% vs 12.5%) (P = 0.001) and postoperative diarrhea (54.1% vs 12.5%) (P = 0.001) in the PDTRIANGLE group. The rates of R0 resection and local recurrence, overall survival, and disease-free survival did not differ significantly between the two groups. CONCLUSION: The TRIANGLE technique is safe, with acceptable postoperative morbidities compared with standardized PD, but it does not improve prognosis for patients with resectable PDAC.

Automated peripancreatic vessel segmentation and labeling based on iterative trunk growth and weakly supervised mechanism.

Peripancreatic vessel segmentation and anatomical labeling are pivotal aspects in aiding surgical planning and prognosis for patients with pancreatic tumors. Nevertheless, prevailing techniques often fall short in achieving satisfactory segmentation performance for the peripancreatic vein (PPV), leading to predictions characterized by poor integrity and connectivity. Besides, unsupervised labeling algorithms usually cannot deal with complex anatomical variation while fully supervised methods require a large number of voxel-wise annotations for training, which is very labor-intensive and time-consuming. To address these two problems, we propose an Automated Peripancreatic vEssel Segmentation and lAbeling (APESA) framework, to not only highly improve the segmentation performance for PPV, but also efficiently identify the peripancreatic artery (PPA) branches. There are two core modules in our proposed APESA framework: iterative trunk growth module (ITGM) for vein segmentation and weakly supervised labeling mechanism (WSLM) for artery labeling. The ITGM is composed of a series of iterative submodules, each of which chooses the largest connected component of the previous PPV segmentation as the trunk of a tree structure, seeks for the potential missing branches around the trunk by our designed branch proposal network, and facilitates trunk growth under the connectivity constraint. The WSLM incorporates the rule-based pseudo label generation with less expert participation, an anatomical labeling network to learn the branch distribution voxel by voxel, and adaptive radius-based postprocessing to refine the branch structures of the labeling predictions. Our achieved Dice of 94.01% for PPV segmentation on our collected dataset represents an approximately 10% accuracy improvement compared to state-of-the-art methods. Additionally, we attained a Dice of 97.01% for PPA segmentation and competitive labeling performance for PPA labeling compared to prior works. Our source codes will be publicly available at https://github.com/ZouLiwen-1999/APESA.

Loss of Claudin-1 incurred by DNMT aberration promotes pancreatic cancer progression.

Pancreatic cancer (PC) is one of the most malignant and deadly tumors of digestive system with complex etiology and pathogenesis. Dysregulations of oncogenes and tumor suppressors due to epigenetic modifications causally affect tumorogenesis; however the key tumor suppressors and their regulations in PC are only partially defined. In this study, we found that Claudin-1 (encoded by CLDN1 gene) was significantly suppressed in PC that correlated with a poor clinical prognosis. Claudin-1 knockdown enhanced PC cell proliferation, migration, and stemness. Pancreatic specific Cldn1 knockout in KPC (LSLKrasG12D/Pdx1-Cre/Trp53R172H+) and KC (LSLKrasG12D/Pdx1-Cre) mice reduced mouse survival, promoted acinar-to-ductal metaplasia (ADM) process, and accelerated the development of pancreatic intraepithelial neoplasia (PanIN) and PC. Further investigation revealed that Claudin-1 suppression was mainly caused by aberrant DNA methylatransferase 1 (DNMT1) and DNMT3A elevations and the resultant CLDN1 promoter hypermethylation, as a DNMT specific inhibitor SGI-1027 effectively reversed the Claudin-1 suppression and inhibited PC progression both in vitro and in vivo in a Claudin-1 preservation-dependent manner. Together, our data suggest that Claudin-1 functions as a tumor suppressor in PC and its epigenetic suppression due to DNMT aberrations is a crucial event that promotes PC development and progression.

Antibiotic prophylaxis with piperacillin-tazobactam reduces organ/space surgical site infection after pancreaticoduodenectomy: a retrospective and propensity score-matched analysis.

BACKGROUND: The occurrence of surgical site infection (SSI) after pancreaticoduodenectomy (PD) is still relatively high. The aim of this retrospective study is to evaluate the efficacy of piperacillin-tazobactam as perioperative prophylactic antibiotic on organ/space SSI for patients underwent PD. METHODS: Four hundred seven consecutive patients who underwent PD between January 2018 and December 2022 were enrolled and analyzed retrospectively. The univariate and multivariate analysis were used to identify independent risk factors of organ/space SSI. Postoperative complications were compared between the two groups according to the use of prophylactic antibiotics by a ratio of 1:1 propensity score-matched (PSM) analysis. RESULTS: Based on perioperative prophylactic antibiotic use, all 407 patients were divided into the ceftriaxone group (n = 192, 47.2%) and piperacillin-tazobactam group (n = 215, 52.8%). The rate of organ/space SSI was 31.2% with the choice of perioperative antibiotics (OR = 2.837, 95%CI = 1.802-4.465, P < 0.01) as one of independent risk factors. After PSM, there were similar baseline characteristics among the groups. Meanwhile, the piperacillin-tazobactam group had a significant lower rate of organ/space SSI compared to the ceftriaxone group both before and after PSM(P < 0.05). CONCLUSIONS: The adoption of piperacillin-tazobactam as perioperative prophylaxis for patients underwent PD reduced organ/space SSI significantly.

The Effect of Perioperative Dexamethasone on Postoperative Complications after Pancreaticoduodenectomy: A Multicenter Randomized Controlled Trial.

OBJECTIVE: This study aimed to evaluate the effect of perioperative dexamethasone on postoperative complications after pancreaticoduodenectomy. BACKGROUND: The glucocorticoid dexamethasone has been shown to improve postoperative outcomes in surgical patients, but its effects on postoperative complications after pancreaticoduodenectomy are unclear. METHODS: This multicenter, double-blind, randomized controlled trial was conducted in four Chinese high-volume pancreatic centers. Adults undergoing elective pancreaticoduodenectomy were randomized to receive either 0.2 mg/kg dexamethasone or a saline placebo as an intravenous bolus within 5 minutes after anesthesia induction. The primary outcome was the Comprehensive Complication Index (CCI) score within 30 days after the operation, analyzed using the modified intention-to-treat principle. RESULTS: Among 428 patients for eligibility, 300 participants were randomized and 265 were included in the modified intention-to-treat analyses. 134 patients received dexamethasone and 131 patients received a placebo. The mean (SD) CCI score was 14.0 (17.5) in the dexamethasone group and 17.9 (20.3) in the placebo group (mean difference, -3.8; 95% CI, -8.4 to 0.7; P=0.100). The incidence of major complications (Clavien-Dindo grade ≥III) (12.7% vs. 16.0%, risk ratio 0.79; 95% CI, 0.44 to 1.43; P=0.439) and postoperative pancreatic fistula (25.4% vs. 31.3%, risk ratio 0.81; 95% CI, 0.55 to 1.19; P=0.286) were not significantly different between the two groups. In the stratum of participants with a main pancreatic duct ≤3 mm (n=202), the CCI score was significantly lower in the dexamethasone group (mean difference, -6.4; 95% CI, -11.2 to -1.6; P=0.009). CONCLUSION: Perioperative dexamethasone did not significantly reduce postoperative complications within 30 days after pancreaticoduodenectomy.

A Weakly Supervised Segmentation Network Embedding Cross-Scale Attention Guidance and Noise-Sensitive Constraint for Detecting Tertiary Lymphoid Structures of Pancreatic Tumors.

The presence of tertiary lymphoid structures (TLSs) on pancreatic pathological images is an important prognostic indicator of pancreatic tumors. Therefore, TLSs detection on pancreatic pathological images plays a crucial role in diagnosis and treatment for patients with pancreatic tumors. However, fully supervised detection algorithms based on deep learning usually require a large number of manual annotations, which is time-consuming and labor-intensive. In this paper, we aim to detect the TLSs in a manner of few-shot learning by proposing a weakly supervised segmentation network. We firstly obtain the lymphocyte density maps by combining a pretrained model for nuclei segmentation and a domain adversarial network for lymphocyte nuclei recognition. Then, we establish a cross-scale attention guidance mechanism by jointly learning the coarse-scale features from the original histopathology images and fine-scale features from our designed lymphocyte density attention. A noise-sensitive constraint is introduced by an embedding signed distance function loss in the training procedure to reduce tiny prediction errors. Experimental results on two collected datasets demonstrate that our proposed method significantly outperforms the state-of-the-art segmentation-based algorithms in terms of TLSs detection accuracy. Additionally, we apply our method to study the congruent relationship between the density of TLSs and peripancreatic vascular invasion and obtain some clinically statistical results.

DTX3L Accelerates Pancreatic cancer Progression via FAK/PI3K/AKT Axis.

DTX3L (Deltex E3 ubiquitin ligase 3 L) is an E3 ubiquitin ligase, a member of the deltex family. It is also known as B-lymphoma and BAL-associated protein (BBAP). DTX3L has been proven to play an important role in various tumor development; however, its role in pancreatic cancer remains unknown. So, we analyzed the DTX3L expression in pancreatic cancer based on the TCGA database and verified it in our samples by qRT­PCR and western blot. We identified that DTX3L was highly expressed in pancreatic cancer, and its expression level was significantly negatively correlated with patients' survival. Using CCK8, colony formation, transwell, and wound healing assays, we found that upregulated DTX3L promotes pancreatic cancer cell proliferation, invasion, and migration. Mechanically, DTX3L combined with EGFR (epidermal growth factor receptor) and prevented the ubiquitination degradation of it. Upregulated EGFR activated the FAK/PI3K/Akt pathway and promoted the progression of pancreatic cancer. Moreover, we found that DTX3L can weaken pancreatic cancer cells' sensitivity to chemotherapy using the orthotopic implant tumor model. In conclusion, DTX3L accelerates pancreatic cancer progression by EGFR dependent FAK/PI3K/Akt pathway activation and may become a potential target for pancreatic cancer treatment.

Vitamin B6 Competition in the Tumor Microenvironment Hampers Antitumor Functions of NK Cells.

Nutritional factors play crucial roles in immune responses. The tumor-caused nutritional deficiencies are known to affect antitumor immunity. Here, we demonstrate that pancreatic ductal adenocarcinoma (PDAC) cells can suppress NK-cell cytotoxicity by restricting the accessibility of vitamin B6 (VB6). PDAC cells actively consume VB6 to support one-carbon metabolism, and thus tumor cell growth, causing VB6 deprivation in the tumor microenvironment. In comparison, NK cells require VB6 for intracellular glycogen breakdown, which serves as a critical energy source for NK-cell activation. VB6 supplementation in combination with one-carbon metabolism blockage effectively diminishes tumor burden in vivo. Our results expand the understanding of the critical role of micronutrients in regulating cancer progression and antitumor immunity, and open new avenues for developing novel therapeutic strategies against PDAC. SIGNIFICANCE: The nutrient competition among the different tumor microenvironment components drives tumor growth, immune tolerance, and therapeutic resistance. PDAC cells demand a high amount of VB6, thus competitively causing NK-cell dysfunction. Supplying VB6 with blocking VB6-dependent one-carbon metabolism amplifies the NK-cell antitumor immunity and inhibits tumor growth in PDAC models. This article is featured in Selected Articles from This Issue, p. 5.

Survival benefit and biomarker of PD-1 inhibitor combination therapy in first-line of advanced biliary tract cancer: A retrospective study.

BACKGROUND: Immune checkpoint inhibitor (ICI) combination therapies have shown promise in the first-line treatment of advanced biliary tract cancer (BTC). However, the best partner remains to be validated. Moreover, progress on biomarkers predicting the efficacy of ICI in BTC is slow. This study aimed to assess the efficacy and investigate reliable predictive biomarkers of programmed cell death protein-1 (PD-1) antibody combination therapy in the first-line treatment of advanced BTC. METHODS: Clinical data from patients with advanced BTC who received chemotherapy or anti-PD-1 combination therapy as first-line were collected. The primary outcome was overall survival (OS). Biomarkers, including peripheral blood inflammation scores, genetic alterations, and tumor microenvironment were investigated. FINDINGS: Sixty-four patients were recruited and divided into four treatment groups: chemotherapy, anti-PD-1 plus chemotherapy, anti-PD-1 plus targeted therapy, and triple group (anti-PD-1 plus chemotherapy and targeted therapy). The median OS was 7.9, 11.3, 12.8, and 28.7 months, respectively. Compared to chemotherapy, mOS significantly prolonged in the triple group (p = 0.031). It showed that patients with five different peripheral blood inflammation scores had significantly prolonged mOS (p < 0.05). Genetic testing results suggested that patients with poor survival all had TP53 mutations and higher levels of KRAS and ERBB2 mutations. Low FOXP3/CD8 ratio was associated with prolonged OS (p = 0.029). With CD4-low, CD8-high, CD56-positive, CD163-high, FOXP3-high and MPO-high in TME as one factor, we calculated PLUS score according to the number of factors. The high-PLUS (>2) group showed significantly superior OS (p = 0.003). INTERPRETATION: First-line anti-PD-1 combination therapy was superior to chemotherapy, and triple therapy significantly improved survival. Peripheral blood immune-inflammation score, FOXP3/CD8 ratio, and PLUS have potential as biomarkers for predicting the efficacy of first-line anti-PD-1 therapy in advanced BTC.

The effect of perioperative of dexamethasone on postoperative complications after pancreaticoduodenectomy (PANDEX): a study protocol for a pragmatic multicenter randomized controlled trial.

BACKGROUND: Pancreaticoduodenectomy (PD) nowadays serves as a standard treatment for patients with disorders of the pancreas, intestine, and bile duct. Although the mortality rate of patients undergoing PD has decreased significantly, postoperative complication rates remain high. Dexamethasone, a synthetic glucocorticoid with potent anti-inflammatory and metabolic effects, has been proven to have a favorable effect on certain complications. However, the role it plays in post-pancreatectomy patients has not been systematically evaluated. The aim of this study is to assess the effect of dexamethasone on postoperative complications after PD. METHODS: The PANDEX trial is an investigator-initiated, multicentric, prospective, randomized, double-blinded, placebo-control, pragmatic study. The trial is designed to enroll 300 patients who are going to receive elective PD. Patients will be randomized to receive 0.2 mg/kg dexamethasone or saline placebo, administered as an intravenous bolus within 5 min after induction of anesthesia. The primary outcome is the Comprehensive Complication Index (CCI) score within 30 days after the operation. The secondary outcomes include postoperative major complications (Clavien-Dindo≥3), postoperative pancreatic fistula (POPF), post-pancreatectomy acute pancreatitis (PPAP), infection, and unexpected relaparotomy, as well as postoperative length of stay, 30-day mortality, and 90-day mortality. DISCUSSION: The PANDEX trial is the first randomized controlled trial concerning the effect of dexamethasone on postoperative complications of patients undergoing PD, with the hypothesis that the intraoperative use of dexamethasone can reduce the incidence of postoperative complications and improve short-term outcomes after PD. The results of the present study will guide the perioperative use of dexamethasone and help improve the clinical management of post-pancreatectomy patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT05567094. Registered on 30 September 30 2022.

CTG-Net: an efficient cascaded framework driven by terminal guidance mechanism for dilated pancreatic duct segmentation.

Pancreatic duct dilation indicates a high risk of various pancreatic diseases. Segmentation for dilated pancreatic duct (DPD) on computed tomography (CT) image shows the potential to assist the early diagnosis, surgical planning and prognosis. Because of the DPD's tiny size, slender tubular structure and the surrounding distractions, most current researches on DPD segmentation achieve low accuracy and always have segmentation errors on the terminal DPD regions. To address these problems, we propose a cascaded terminal guidance network to efficiently improve the DPD segmentation performance. Firstly, a basic cascaded segmentation architecture is established to get the pancreas and coarse DPD segmentation, a DPD graph structure is build on the coarse DPD segmentation to locate the terminal DPD regions. Then, a terminal anatomy attention module is introduced for jointly learning the local intensity from the CT images, feature cues from the coarse DPD segmentation and global anatomy information from the designed pancreas anatomy-aware maps. Finally, a terminal distraction attention module which explicitly learns the distribution of the terminal distraction regions is proposed to reduce the false positive and false negative predictions. We also propose a new metric called tDice to measure the terminal segmentation accuracy for targets with tubular structures and two other metrics for segmentation error evaluation. We collect our dilated pancreatic duct segmentation dataset with 150 CT scans from patients with five types of pancreatic tumors. Experimental results on our dataset show that our proposed approach boosts DPD segmentation accuracy by nearly 20% compared with the existing results, and achieves more than 9% improvement for the terminal segmentation accuracy compared with the state-of-the-art methods.

The role of preoperative biliary drainage on postoperative outcome after pancreaticoduodenectomy in patients with obstructive jaundice.

Background: The role of preoperative biliary drainage (PBD) on obstructive jaundice patients is still controversial. The aim of this retrospective study is to clarify the effect of PBD on postoperative outcomes of pancreaticoduodenectomy (PD) and explore a reasonable PBD strategy for periampullary carcinomas (PAC) patients with obstructive jaundice before surgery. Methods: A total of 148 patients with obstructive jaundice who underwent PD were enrolled in this research and divided into drainage group and no-drainage group according to whether they received PBD. Patients who received PBD were classified into long-term group (>2 weeks) and short-term group (≤2 weeks) according to PBD duration. The clinical data of patients were statistically compared between groups to explore the influence of PBD and its duration. Analysis of pathogens in bile and peritoneal fluid was performed to probe the role of bile pathogens in opportunistic pathogenic bacterial infection after PD. Results: Of all, 98 patients underwent PBD. The mean duration between drainage and surgery was 13 days. Regarding postoperative outcomes, the incidence of postoperative intra-abdominal infection was significantly higher in the drainage group than the no-drainage group (P=0.026). In patients with total bilirubin (TB) less than 250 µmol/L, postoperative intra-abdominal infection was more frequently observed in the drainage group compared to the no-drainage group (P=0.022). Compared to the short-term drainage group, the proportion of positive ascites culture was significantly higher in the long-term drainage group (P=0.022). There were no statistically significant differences in postoperative complications between short-term group and no-drainage group. The most frequent pathogens detected in bile were Klebsiella pneumoniae, hemolytic Streptococcus and Enterococcus faecalis. The most commonly detected pathogens in peritoneal fluid were Klebsiella pneumoniae, Enterococcus faecalis and Staphylococcus epidermidis which appeared to have a high agreement with pathogens in preoperative bile cultures. Conclusions: Routine PBD should not be performed in obstructive jaundice PAC patients with TB less than 250 µmol/L. For patients with indications for PBD, the drainage duration should be controlled within 2 weeks. Bile bacteria may represent a major source of opportunistic pathogenic bacteria infection after PD.

Clinical Validation of the Comprehensive Complication Index in a Pancreaticoduodenectomy Cohort.

INTRODUCTION: Although the Clavien-Dindo classification (CDC) is the most widely utilized method for quantifying surgical complications, it fails to properly capture all events. To address this, the comprehensive complication index (CCI) was introduced. The purpose of this study was to compare the CCI and CDC as predictors of postoperative length of stay (PLOS) and total hospitalization costs in patients undergoing pancreaticoduodenectomy (PD). METHODS: Data were collected from February 2018 to February 2021. Complications were graded on the CDC scale and the CCI was calculated for each patient. The correlations between CDC and CCI with PLOS and hospitalization costs were compared. Linear analyses were performed to identify factors associated with PLOS and costs. RESULTS: 291 patients were enrolled with an average age of 61.2 years. 286 of them developed postoperative complications at CDC grade 1 (17.8%), 2 (59.9%), 3a (13.4%), 3b (4.5%), 4 (2.1%), and 5 (0.6%). Median CCI of the study cohort was 30.8. Spearman's correlation analysis showed the CDC and CCI were significantly correlated with PLOS and hospitalization costs, but the CCI showed a stronger correlation with PLOS (+0.552 day of stay for each additional CCI point; CCI: ρ = 0.663 vs. CDC: ρ = 0.581; p = 0.036). There were no significant differences in the correlations between total hospitalization costs and the CDC or CCI (CCI: ρ = 0.566 vs. CDC: ρ = 0.565; p = 0.78). CONCLUSION: CCI is an accurate tool for quantifying morbidities after PD and shows a stronger correlation with PLOS compared with the CDC.

The Effect of immunonutrition in patients undergoing pancreaticoduodenectomy: a systematic review and meta-analysis.

BACKGROUND: Pancreaticoduodenectomy (PD) is a complex and traumatic abdominal surgery with a high risk of postoperative complications. Nutritional support, including immunonutrition (IMN) with added glutamine, arginine, and ω-3 polyunsaturated fatty acids, can improve patients' prognosis by regulating postoperative inflammatory response. However, the effects of IMN on PD patients' outcomes require further investigation. METHODS: PMC, EMbase, web of science databases were used to search literatures related to IMN and PD. Data such as length of hospital stay, infectious complications, non-infectious complications, postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE), mortality, systemic inflammatory response syndrome (SIRS) duration, IL-6, and C-reactive protein (CRP) were extracted, and meta-analyses were performed on these data to study their pooled results, heterogeneity, and publication bias. RESULTS: This meta-analysis involved 10 studies and a total of 572 patients. The results showed that the use of IMN significantly reduced the length of hospital stay for PD patients (MD = -2.31; 95% CI = -4.43, -0.18; P = 0.03) with low heterogeneity. Additionally, the incidence of infectious complications was significantly reduced (MD = 0.42; 95% CI = 0.18, 1.00, P = 0.05), with low heterogeneity after excluding one study. However, there was no significant impact on non-infectious complications, the incidence of POPF and DGE, mortality rates, duration of SIRS, levels of IL-6 and CRP. CONCLUSION: The use of IMN has been shown to significantly shorten hospital stays and decrease the frequency of infectious complications in PD patients. Early implementation of IMN is recommended for those undergoing PD. However, further research is needed to fully assess the impact of IMN on PD patients through larger and higher-quality studies.

Copper Increases the Sensitivity of Cholangiocarcinoma Cells to Tripterine by Inhibiting TMX2-Mediated Unfolded Protein Reaction Activation.

Chemotherapy-induced adaptive resistance is a significant factor that contributes to low therapeutic efficacy in tumor cells. The unfolded protein response (UPR) is a key mechanism in the development of drug resistance and serves as a critical reactive system for endoplasmic reticulum stress. Cu(II) can reduce the abundance of 60S ribosomal subunits and inhibit rRNA processing, leading to a decrease in the translation efficiency of the GRP78/BiP mRNA, which serves as a primary sensor for UPR activation. In this study, CuET-Lipid@Cela, composed of CuET and tripterine (Cela), demonstrates a significant synergistic antitumor effect on cholangiocarcinoma (CCA) cells. RNA-Seq is used to investigate the underlying mechanism, which suggests that the transmembrane protein 2 (TMX2) gene may be crucial in Cu(II) regulation of UPR by inhibiting the activation of GRP78/BiP and PERK/eIF2α. The synergistic antitumor efficacy of CuET-Lipid@Cela via inhibition of TMX2 is also confirmed in a myrAKT/YapS127A plasmid-induced primary CCA mouse model, providing new insights into the reversal of acquired chemotherapy-induced resistance in CCA.

PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with BRPC/LAPC: A biomolecular exploratory, phase II trial.

This is a phase II study of PD-1 blockade plus chemoradiotherapy as preoperative therapy for patients with locally advanced or borderline resectable pancreatic cancer (LAPC or BRPC, respectively). Twenty-nine patients are enrolled in the study. The objective response rate (ORR) is 60%, and the R0 resection rate is 90% (9/10). The 12-month progression-free survival (PFS) rate and 12-month overall survival (OS) rate are 64% and 72%, respectively. Grade 3 or higher adverse events are anemia (8%), thrombocytopenia (8%), and jaundice (8%). Circulating tumor DNA analysis reveals that patients with a >50% decline in maximal somatic variant allelic frequency (maxVAF) between the first clinical evaluation and baseline have a longer survival outcome and a higher response rate and surgical rate than those who are not. PD-1 blockade plus chemoradiotherapy as preoperative therapy displays promising antitumor activity, and multiomics potential predictive biomarkers are identified and warrant further verification.

Effect of inferior vena cava respiratory variability-guided fluid therapy after laparoscopic hepatectomy: a randomized controlled clinical trial.

BACKGROUND: After major liver resection, the volume status of patients is still undetermined. However, few concerns have been raised about postoperative fluid management. We aimed to compare gut function recovery and short-term prognosis of the patients after laparoscopic liver resection (LLR) with or without inferior vena cava (IVC) respiratory variability-directed fluid therapy in the anesthesia intensive care unit (AICU). METHODS: This randomized controlled clinical trial enrolled 70 patients undergoing LLR. The IVC respiratory variability was used to optimize fluid management of the intervention group in AICU, while the standard practice of fluid management was used for the control group. The primary outcome was the time to flatus after surgery. The secondary outcomes included other indicators of gut function recovery after surgery, postoperative length of hospital stay (LOS), liver and kidney function, the severity of oxidative stress, and the incidence of severe complications associated with hepatectomy. RESULTS: Compared with patients receiving standard fluid management, patients in the intervention group had a shorter time to anal exhaust after surgery (1.5 ±â€Š0.6 days vs. 2.0 ±â€Š0.8 days) and lower C-reactive protein activity (21.4 [95% confidence interval (CI): 11.9-36.7] mg/L vs. 44.8 [95%CI: 26.9-63.1] mg/L) 24 h after surgery. There were no significant differences in the time to defecation, serum concentrations of D -lactic acid, malondialdehyde, renal function, and frequency of severe postoperative complications as well as the LOS between the groups. CONCLUSION: Postoperative IVC respiratory variability-directed fluid therapy in AICU was facilitated in bowel movement but elicited a negligible beneficial effect on the short-term prognosis of patients undergoing LLR. TRIAL REGISTRATION: ChiCTR-INR-17013093.

Predictive Value of Body Composition Parameters for Postoperative Complications in Patients Who Received Pancreaticoduodenectomy.

INTRODUCTION: Sarcopenia and visceral obesity have been identified as risk factors for postoperative complications following hepatobiliary and colon surgery. However, the correlation between body composition parameters and morbidity following pancreatectomy remains unclear. This study aimed to assess the predictive value of body composition parameters measured from preoperative CT images for postoperative complications following pancreaticoduodenectomy (PD). METHODS: A retrospective study of patients who underwent PD between January 2018 and January 2021 was performed. Areas of subcutaneous adipose tissue, visceral adipose tissue, total abdominal muscle area, and mean muscle radio-attenuation were measured from preoperative CT images. Postoperative complications were categorized according to the Clavien-Dindo classification, and comprehensive complication index (CCI) scores were calculated. Logistic regression analysis was performed to identify factors associated with clinically relevant postoperative pancreatic fistula (CR-POPF) and high CCI score (≥26.2). RESULTS: From the data collected on 129 study patients, sarcopenia, visceral obesity, and myosteatosis were detected in 47 (36.4%), 38 (29.4%), and 50 (38.7%) patients, respectively. CR-POPF developed in 51 (39.5%) patients, the overall median CCI score was 30.8 (22.6-36.2), and high CCI scores were identified in 70 (54.3%) patients. Multivariate analysis indicated sarcopenia and visceral obesity were independent risk variables for CR-POPF. Preoperative sarcopenia, visceral obesity, age, preoperative biliary drainage, and a positive culture of postoperative drainage were predictors of high CCI scores. CONCLUSION: Sarcopenia and visceral obesity were significant predictors of CR-POPF and high CCI score. Preoperative body composition assessment by CT images may help identify high-risk patients who undergo PD.

Effectiveness and safety of path-based analgesic regimens designed by clinical pharmacists based on the type of biliary and pancreatic surgery.

WHAT IS KNOWN AND OBJECTIVE: As the incidence of postoperative pain in patients with biliary and pancreatic diseases has gradually increased, how to control postoperative pain has received increasing research attention. By reading pain management guidelines and multidisciplinary communication and cooperation, clinical pharmacists designed multi-mode analgesia regimens based on surgical types, in order to provide strong evidence for the effectiveness and safety of postoperative analgesia regimens and better serve patients. METHODS: Data from biliary or pancreatic surgery performed at Nanjing Drum Tower Hospital from 2019 to 2021 were collected. Take October 2020 as the time point to compare the outcomes before and after the implementation of the path-based postoperative analgesic regimens. The primary outcomes were NRS pain scores, sleep quality, and incidence of adverse reactions. Length of stay was a secondary outcome. RESULTS AND DISCUSSION: A total of 268 and 239 patients were enrolled in the study and control groups, respectively. Four path-based postoperative analgesic management regimens significantly reduced patients' static and dynamic NRS scores in the 24 h (p < 0.05). The patients' sleep quality were better than controls (p > 0.05). The incidence of adverse reactions and the length of stay in the study group were numerically lower than controls. Moderate analysis indicated that four analgesia regimens are more precise and better meet actual clinical needs. WHAT IS NEW AND CONCLUSION: Effective and safe postoperative pain management is particularly important for clinical purposes. Path-based postoperative analgesia regimens based on different types of surgery overcome the disadvantages of overly broad and generalized traditional guidelines, which play an important role in providing personalized and precise clinical services. Further, study findings provide evidence that four path-based analgesic regimens can reduce postoperative pain and reduce the length of hospital stay, which may provide a better direction for clinical postoperative pain management.

Therapeutic effect and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression level in unresectable pancreatic cancer.

Aim: We aimed to evaluate the efficacy and safety of individualized chemotherapy combined with sequential immunotherapy based on BRCA1 mRNA expression in unresectable pancreatic cancer. Methods: The expression of BRCA1 mRNA in tumor tissues of 25 patients with pancreatic cancer was detected in this retrospective study. Patients in the medium and high expression groups were treated with paclitaxel-based chemotherapy: albumin paclitaxel 125mg/m2, gemcitabine 1g/m2, day 1. Patients in the low expression group were treated with oxaliplatin-based chemotherapy: oxaliplatin 85mg/m2, gemcitabine 1g/m2, day 1. Sequential GM-CSF and IL-2 immunotherapy were applied. Patient condition, treatment efficacy and safety were assessed every 4 cycles. Results: A total of 25 patients were enrolled in the study. All of them were observed for toxic side effects and 24 of them were evaluated for efficacy. The median overall survival and median progression-free survival were 11.9 months and 6.3 months. The disease control rate was 91.7%, of which 37.5% (9/24) patients achieved partial remission (PR), 54.2% (13/24) patients achieved stable disease (SD) and 8.3% (2/24) patients were assessed as progressive disease(PD). Of the 15 patients with medium or high expression in BRCA1 mRNA, 7 achieved PR and 8 achieved SD. Of the 9 patients with low BRCA1 mRNA expression, 2 achieved PR, 5 achieved SD and 2 had PD. The proportion of eosinophils in the blood of some patients with good therapeutic effects was significantly higher than that before treatment. Hematological and non-hematological toxicity during the treatment were mostly grade 1~2. The two most common grade 3 to 4 adverse events were fever and thrombocytopenia. Conclusion: Our results suggest that individualized selection of chemotherapy combined with sequential immunotherapy according to BRCA1 mRNA expression level in unresectable pancreatic cancer could control the disease and have controllable adverse reactions.